ISG56 is a negative-feedback regulator of virus-triggered signaling and cellular antiviral response
ISG56 is a negative-feedback regulator of virus-triggered signaling and cellular antiviral response
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ISG56 是病毒触发信号传导和细胞抗病毒反应的负反馈调节因子
DOI：
10.1073/pnas.0900818106
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发表时间：
2009-05-12
影响因子：
11.1
通讯作者：
Shu, Hong-Bing
中科院分区：
文献类型：
--
作者：
Li, Ying;Li, Chao;Shu, Hong-Bing
干扰素刺激基因56（ISG 56）是最早被鉴定的由病毒和I型干扰素诱导的蛋白质之一。在这项研究中，我们将ISG 56鉴定为与MITA相关的病毒诱导蛋白，MITA是一种参与病毒触发的I型干扰素诱导的衔接蛋白。ISG 56的过表达抑制仙台病毒触发的IRF 3、NF-κB和IFN-β启动子的激活，而ISG 56的敲低具有相反的作用。一致地，ISG 56的过表达逆转了胞质聚（I：C）诱导的水泡性口炎病毒（VSV）复制的抑制，而ISG 56的敲低抑制了VSV复制。竞争性免疫共沉淀实验表明，ISG 56破坏了MITA和VISA或TBK 1之间的相互作用，这两种组分是病毒触发的IFN信号通路中的两种组分。这些结果表明，ISG 56是病毒触发的I型IFN诱导和细胞抗病毒应答的负反馈调节的介质。
IFN-stimulated gene 56 (ISG56) is one of the first identified proteins induced by viruses and type I IFNs. In this study, we identified ISG56 as a virus-induced protein associated with MITA, an adapter protein involved in virus-triggered induction of type I IFNs. Overexpression of ISG56 inhibited Sendai virus-triggered activation of IRF3, NF-κB, and the IFN-β promoter, whereas knockdown of ISG56 had opposite effects. Consistently, overexpression of ISG56 reversed cytoplasmic poly(I:C)-induced inhibition of vesicular stomatitis virus (VSV) replication, whereas knockdown of ISG56 inhibited VSV replication. Competitive coimmunoprecipitation experiments indicated that ISG56 disrupted the interactions between MITA and VISA or TBK1, two components in the virus-triggered IFN signaling pathways. These results suggest that ISG56 is a mediator of negative-feedback regulation of virus-triggered induction of type I IFNs and cellular antiviral responses.